The overall objective of this proposal is to study the epigenetic factors that favor, modify or inhibit the expression of the malignant phenotype of undifferentiated embryonic cells and stem cells of teratocarcinoma. To this end teratocarcinomas are produced from 7-day mouse embryos transplanted under the kidney of immunologically compatible recipients. It has been shown that the yield of malignant tumors depends on host-related and embryo-related factors which either promote or inhibit teratocarcinogenesis. Among the host-related factors, the immune factors play a significant role. The genome of the embryo and the maternally transmitted factors also influence the teratocarcinogenesis. The malignant stem cells of murine teratocarcinomas, like their putative precursors in the embryo, express on their surface a fucopentaose moiety which can be recognized with monoclonal antibodies. Upon differentiation of either embryonic or tumor cells, this surface marker disappears from the cell surface. Antibodies recognizing this stage-specific embryonic antigen react with many tissues in the adult mouse and even humans and are thus not restricted or uniquely specific for mouse embryonal carcinoma cells. Human embryonal carcinoma cells, on the other hand, display surface characteristics which make them distinct from the equivalent mouse tumor cells.